One of the innovative aspects of the Center application is the ability to examine the effects of pharmacological agents across three platforms: i) animal models which allow early screening and exploration of neuronal and cellular mechanisms;ii) non-clinical human model which provide opportunity for ascertaining an early human signal of potential efficacy of a compound for cognition and/or negative symptom phenotypes in the absence of the usual confounds associated with clinical cohorts (e.g., chronicity, psychosis, antipsychotic drugs);and iii) clinical trial confirming the validity of this approach. The Research Methods Core is responsible for developing a battery of biomarkers to be used in human studies (Projects #2 and #3). In addition, the Core will provide expertise, staff and facilities in order for the Projects #2 and #3 can carry out the proposed drug studies. The Core will develop and provide analytic strategy that evaluates effects of drugs within each of the 3 projects (1 preclinical and 2 human), and relates effects across the three set of studies using the same drugs. The Research Method Core will maintain an extensive interaction with the Pre-clinical Studies Core. The Core will interact with the Operations and Clinical Assessment Core around data management, and issues related to design and statistics.